Abstract
Objectives:
A transgenic murine model for thyroid cancer was used to evaluate the effectiveness of molecularly targeted ratiometric activatable cell-penetrating peptides (RACPPs) for surgical navigation. We will analyze the implementation of fluorescence guided surgery in this model and discuss future applications.
Methods:
Thirteen transgenic BRAFV600E mice were studied prospectively. Seven were injected with RACPP, and 4 were injected with saline (controls). Pre- and postoperative laryngoscopy was used to assess vocal cord function. Total thyroidectomy was performed with microscopic white-light visualization. Fluorescence imaging of the post-thyroidectomy field was performed, and fluorescent tissue was removed for pathology. One surgeon carried out all procedures. Data underwent blinded review by a board certified pathologist and a laryngologist.
Results:
There were 7 successful fluorescence guided surgical procedures and four successful controls. Average operative times were 15.8 (RACPP) and 14 minutes (controls). RACPPs improved thyroid tumor visualization with an average intensity ratio of 9.1, versus 1.5 with white-light alone. Intact function was present in 12 of 12 vocal cords in the study group and 1 of 2 vocal cords of the controls. Postoperatively, 5 RACPP animals showed fluorescent signal, but on histology there was no tumor. Thyroid tumor was present in the final surgical beds of 3 animals, 2 RACPP animals, and 1 control.
Conclusions:
In this transgenic murine model of papillary thyroid cancer, RACPPs improved surgical visualization without compromising post-resection vocal cord function. There was no proven benefit for completeness of resection. Surgical molecular guidance with RACPPs warrants further study.
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